Cadmium: in vivo measurement in smokers and nonsmokers.

Absolute amounts of cadmium (in milligrams) in the left kidney and concentrations of cadmium (micrograms per gram) in the liver were measured in vivo in 20 healthy adult male volunteers. Organ cadmium levels of smokers were significantly elevated above those of nonsmokers. No relationship was evident between body stores of cadmium (liver and kidney) and cadmium or beta 2-microglobulin in urine or blood. The average total body burden of cadmium in man at age 50 is estimated to be 19.3 milligrams for nonsmokers and 35.5 milligrams for smokers (38.7 pack-year smoking history). Biological half-time for the whole body was, on average, 15.7 years (10- to 33-year range). Dietary absorption was 2.7 micrograms per day. Cigarette smoking resulted in the absorption of 1.9 micrograms per pack.

Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study.

The physical characteristics of Sn-117m combined with the biodistribution of the compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA) suggest that it should be an excellent agent for the palliation of pain from bony metastases. Prior work has established the dosimetry and the safety for the material in human beings. The presence of low-energy conversion electrons should result in the relative sparing of the bone marrow while delivering a high radiation dose to sites of bony metastatic disease. Forty-seven patients with painful bone metastases from various malignancies were treated with Sn-117m DTPA. The patients were assigned to five different dose levels ranging from 2.64 to 10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of pain diaries, performance scores, analgesic requirements, blood chemistries, and hematological assessment. Three patients received a second treatment. There was an overall response rate for relief of pain of 75% (range, 60-83%) in the 40 treatments that could be evaluated. No correlation was apparent in this limited series between response rate and the five dose levels used. The relief was complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15 days with doses < or = 5.29 MBq/kg and 5 +/- 3 days with doses > or = 6.61 MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade 3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and safe radiopharmaceutical for palliation of painful bony metastases. A large-scale trial is warranted to evaluate it in comparison to other similar agents.

Hydroxyproline peptides and bone mass in postmenopausal and osteoporotic women.

Total and nondialyzable hydroxyproline excretion was measured in 59 postmenopausal women and 68 women with spinal osteoporosis. Hydroxyproline excretion was similar in both groups of women and the hypothesis that hydroxyproline excretion is normally distributed could not be rejected for either group. No relationship was found between hydroxyproline excretion (total and percentage of nondialyzable) and body weight, height, body surface area, or total body calcium or bone mineral content of the radius, or these latter values normalized for age, sex, and body size. There was no difference in hydroxyproline excretion in osteoporotic women who took supplemental calcium as compared to those that did not. These data fail to provide any evidence that bone turnover in osteoporotic women differs from that in younger postmenopausal women, or that osteoporosis arises from a subpopulation of women with rapid bone loss.

Effects of growth hormone in osteoporosis.

The effect of chronic administration of growth hormone (GH) to osteoporotic patients was studied using the techniques of total body neutron activation analysis, whole body counting, calcium tracer kinetics, photon absorptiometry, quantitative microradiography, and urinary hydroxyproline. Two dosage schedules were utilized for six months each: 2 units daily and 0.2 w3/4 units of GH daily (where W represents body weight expressed in kg). The lower dosage (2 units) did not produce any appreciable change in the indices studied. Following the higher dose, no evidence of any anabolic effect was apparent in most patients (i.e., no increase in total body levels of Ca, Na, K, P, or Cl). Increases were noted in the urinary calcium excretion rate and in the urinary hydroxyproline excretion. Bone mineral content decreased. The bone biopsies displayed an increase in bone formation and resorption surfaces in response to treatment, but these changes were not statistically significant. It may be concluded that under the conditions of this study, GH administration did not result in an increment in skeletal mass. Several side effects that are characteristic of acromegaly were observed, including hyperglycemia, hypertension, arthralgia, and the carpal tunnel syndrome. Because of the lack of demonstrated benefit and the associated complications of therapy, GH administration does not appear to be of value in the treatment of osteoporosis.

False-positive FDG-PET imaging of the thymus of a child with Hodgkin's disease.

During the evaluation of a child who had completed treatment for Hodgkin's disease, a PET study strongly suggested recurrent disease in the mediastinum. Biopsies were obtained and revealed normal thymic tissue only, with no evidence of recurrent disease. The ongoing difficulty in establishing accurate disease status in patients treated for Hodgkin's disease is discussed, along with recommendations for treating pediatric patient populations.

Phonton absorptiometry and skeletal mass in the treatment of osteoporosis.

Thirty-six osteoporotic patients who underwent several therapeutic regimes were studied on two occasions by photon absorptiometry and total-body neutron activation analysis (TBNAA). These determinations were made at a mean interval of 8.9 plus or minus 0.8 months. The 8-cm radial site was chosen for the photon absorptiometry which was performed with the Norland-Instruments Densitometer. Mean initial bone mineral content (BMC) was 0.724 plus or minus 0.069 gm/cm and mean bone width was 1.235 plus or minus 0.072 cm. The mean percent change in BMC (%deltaBMC) was 1.02 plus or minus 4.2. The initial total-body calcium (TBCa) as determined by TBNAA was reduced when compared with values that would be expected from empirically derived formulas. The mean percent change in TB-Ca (%deltaTB-Ca) was -3.2 plus or minus 4.7. Most patients displayed a change in BMC and TB-Ca that was at least 2 s.d. greater than the precision of the methods used (%deltaTB-Ca greater than 2). No relationship was found between the deltaBMC and the deltaTB-Ca (r = 0.17). These findings suggest that changes in the radical BMC at the 8-cm site cannot be extrapolated to indicate changes in skeletal mass in response to treatment of osteoporosis. Whether photon absorptiometry at other sites or at multiple sites provides a closer relationship to changes in skeletal mass (TB-Ba) remains to be determined.

Scintigraphic evaluation of postoperative complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is gaining popularity as an alternative to standard open cholecystectomy. At our institution, approximately 400 laparoscopic cholecystectomies have been performed since May 1989. The frequency of major postoperative complications has been approximately 1.5% (6 out of 400 cases). The most common complications have been biliary tree injury, bile leak, and retained stone. We present three patients who developed postoperative complications that were properly diagnosed on 99mTc-DISIDA cholescintigraphy. Our report indicates that 99mTc-DISIDA scintigraphy facilitates the rapid and precise diagnosis of bile leaks in patients with abdominal pain and/or hyperbilirubinemia following laparoscopic cholecystectomy.

Total-body sodium and sodium excess.

Total-body levels of sodium (TBNa), chlorine (TBCl), calcium (TBCa), and potassium (TBK) were measured by neutron activation and analysis of results by whole body counting in 66 postmenopausal women. The relationship between TBNa, and TBCl, TBK, and TBCa on the one hand, and height and weight on the other, were found to compare with those previously reported. The hypothesis that TBNa and TBCl are distributed normally could not be rejected. The sodium excess (Naes) is defined as the sodium that is present in excess of that associated with the extracellular fluid (chlorine) space; the Naes approximates nonexchangeable bone sodium. In these 66 postmenopausal women, and in patients with different endocrinopathies previously described, the values of Naes did not differ from the normal values except in the thyrotoxicosis patients, where they were decreased. A close relationship between Naes and TBCa was maintained in the endocrinopathies studied. This relationship was found in conditions accompanied by either an increment or a loss of skeletal mass. It appear

Radiographic morphometry and osteopenia in spinal osteoporosis.

Measurements of bone mineral content and total-body calcium, normalized and expressed as ratios, were compared with radiographic morphometry in 45 women who had spinal osteoporosis. The radiographic indices examined included the femoral score, the femoral trabecular pattern, the biconcavity and metacarpal indices, and the total peripheral score. Both ratios and all the radiographic indices except the femoral trabecular pattern were found to be related to the number of dorsal spine fractures. The relationships observed support the following conclusions: (A) the femoral score and the metacarpal index are related to the degree of osteopenia; (B) the biconcavity index reflects the extraskeletal factors that are pathogenic in spinal osteoporosis; (C) a reduced femoral trabecular pattern index is associated with spinal osteoporosis, although this measurement is not related to the degree of osteopenia; and (D) it may be imprudent to diagnose osteoporosis from the presence of lumbar compression fractures.

Effect of PEEP on regional ventilation and perfusion in the mechanically ventilated preterm lamb.

Improvement of gas exchange through closer matching of regional ventilation (V) and lung perfusion (Q) with the application of positive end-expiratory pressure (PEEP) was evaluated in vivo in six mechanically ventilated preterm lambs (107-126 days/145 days gestation). Changes in V and Q were determined from in vivo scintigraphic measurements in four lung regions with inhaled radioactive 81mKr, and infused 81mKr/dextrose and/or [99mTc]MAA as PEEP was applied at 2, 4, and 6 cm H2O in each animal. Dynamic compliance varied between 0.02 and 0.40 ml/cm H2O, which was consistent with surfactant deficiency. As PEEP was increased, the regional distribution of Q shifted from the rostral to the caudal lung regions (p less than 0.02 to less than 0.05), while that of V remained unchanged. Regional V/Q matching improved together with a trend towards improvement of arterial blood gases as PEEP was increased from 2 to 4 cm H2O. Pulmonary scintigraphy offers a noninvasive methodology for the quantitative assessment of regional V and Q matching in preterm lambs and may be clinically applicable to ventilated neonates.

Comparative nigrostriatal dopaminergic imaging with iodine-123-beta CIT-FP/SPECT and fluorine-18-FDOPA/PET.

UNLABELLED: SPECT imaging of the dopamine transporter is now an alternative to PET in the quantification of nigrostriatal dopaminergic function. We compared [123I] beta CIT-FP/SPECT and [18F]FDOPA/PET in the assessment of nigrostriatal dopaminergic function in Parkinson's disease (PD) and normal aging. METHODS: We studied 12 mildly affected PD patients (mean age: 61.0 +/- 13.2 yr; H&Y Stage I-II) with both [123I] beta CIT-FP and [18F]FDOPA. Fifteen normal volunteers (mean age: 45.5 +/- 22.1 yr) served as controls for both tracers. We measured the striato-occipital ratio (SOR) for both tracers at approximately 100 min postinjection. RESULTS: We found a highly significant correlation between SOR measures obtained for both tracers (r = 0.79, p < 0.0001). In normal volunteers a significant age-related decline in striatal uptake was noted with [123I] beta CIT-FP (r = -0.56, p < 0.04) but not with [18F]FDOPA. SOR values for both tracers discriminated PD patients from controls with comparable accuracy (F[1,25] = 52.1 and 53.0, p < 0.0001 for [123I] beta CIT-FP and [18F]FDOPA, respectively). UPDRS motor ratings correlated with SOR values obtained by both imaging techniques (r = -0.69 and -0.60, p < 0.04 for [123I] beta CIT-FP and [18F]FDOPA, respectively). CONCLUSION: These results indicate that [123I] beta CIT-FP/SPECT can provide quantitative descriptors of presynaptic dopaminergic function comparable to those obtained with [18F]FDOPA/PET.

Input functions for 6-[fluorine-18]fluorodopa quantitation in parkinsonism: comparative studies and clinical correlations.

UNLABELLED: PET has been used to quantify striatal 6-[18F]fluoro-L-dopa (FDOPA) uptake as a measure of presynaptic dopaminergic function. Striatal FDOPA uptake rate constants (Ki) can be calculated using dynamic PET imaging with measurements of the plasma FDOPA input function determined either directly or by several estimation procedures. METHODS: We assessed the comparative clinical utility of these methods by calculating the striato-occipital ratio (SOR) and striatal Ki values in 12 patients with mild to moderate PD and 12 age-matched normal volunteers. The plasma FDOPA time-activity curve (KiFD); the plasma 18F time-activity curve (KiP); the occipital time-activity curve (KiOCC); and a simplified population-derived FDOPA input function (KiEFD) were used to calculate striatal Ki. RESULTS: Mean values for all striatal Ki estimates and SOR were significantly lower in the PD group. Although all measured parameters discriminated PD patients from normals, KiFD and KiEFD provided the best between-group separation. KiFD, KiEFD and KiOCC measures correlated significantly with quantitative disease severity ratings, although KiFD predicted quantitative clinical disability most accurately. CONCLUSION: These results suggest that KiFD may be an optimal marker of the parkinsonian disease process. KiEFD may be a useful alternative to KiFD for most clinical research applications.

Hepatobiliary scintigraphy after biliary tract surgery.

Hepatobiliary scintigraphy provides a rapid, noninvasive, accurate means of assessing patients after biliary tract surgery. This is especially important, given the high incidence of biliary and enteric diseases. In this review article, the role of radionuclide imaging in postcholecystectomy and postgastroenteric surgery patients will be examined, as well as following invasive procedures and trauma.

Combination therapy for osteoporosis with estrogen, fluoride, and calcium.

Nine women with postmenopausal spinal osteoporosis were treated with combination therapy consisting of estrogen, fluoride, and calcium. Their data were compared with those of a control group treated with fluoride, and calcium without estrogen. Bone mass was measured about every six months by photon absorptiometry (bone mineral content/bone width (BMC/BW)] and total-body neutron activation analysis [total-body calcium (TB Ca)]. Time-trend analysis revealed positive slopes for TB Ca (P = 0.002) and BMC/BW (P = N.S.) for the combination therapy group. The change in BMC/BW in the combination therapy group was significantly different from the response in the fluoride - calcium group. These data suggest that combination therapy may be successful in increasing bone mass in postmenopausal osteoporosis. A clinical trial to establish efficacy and examine risk/benefit ratios should be performed.

Absence of an effect of chronic administration of growth hormone on serum lipids.

Human growth hormone (hGH) was administered to a group of osteoporotic patients at two dosage levels for a period of 6 mo each. The first dose employed was 2 units subcutaneously daily, and the second dose was 0.2W-3/4 units (where W is body weight expressed in kg) daily. There was no significant change in serum-cholesterol or triglyceride concentration despite the production of hyperglycemia and soft-tissue swelling on the higher dosage regimen. A number of factors may account for the conflict between our findings and a previous report in which hGH administration had a lypocholesterolemic, hyperglyceridemic effect. These factors include differences in sex, age, dosage, and duration of treatment. Nonetheless, it is clear that from a therapeutic vantage, even if hGH were readily available, it would not be a useful hypocholesterolemic agent.

Total body sodium and chlorine in normal adults.

Absolute levels of total body sodium (TBNa) and total body chlorine (TBCl) were determined in 81 normal adults (39 males, 42 females) by means of total body neutron activation analysis (TBNAA). The ages of the subjects ranged from 30 to 90 yr. The mean values for both TBNa and TBCl remained relatively constant throughout the age span studied for males, but decreased slightly for females over 60 yr of age. In order for the absolute measurements of Na and Cl to be of clinical value, the values must be compared to a predicted value based on the sex and body habitus of the individual. Normalization of TBNa values relative to body dimensions (weight, height, body surface area) were evaluated. In addition, TBNa was related to total body calcium (TBCa), which reflects skeletal mass, and TBK, which reflects muscle, or lean body mass. Normalization in terms of a linear combination of the TBCa and TBK was found to be the most satisfactory of all those studied. Sodium excess, NaES, defined as the amount of body sodium (mEq) in excess of body chlorine (mEq) was determined. Sodium excess correlated well with total body calcium. Values for total body sodium and chlorine obtained in the present study were compared with values previously reported in the literature.

Comparative skeletal mass and radial bone mineral content in black and white women.

The age-related changes in both skeletal mass and muscle mass were directly measured in normal black women ages 30-80 yr. The levels of total-body calcium (TBCa) were determined with the use of in vivo neutron activation. The muscle mass was measured by wholebody counting of 40K. In the same population, the bone mineral content of the radius was measured using a photon absorptiometric technique. Although there was no significant difference in stature, black women had a greater skeletal mass and bone mineral content of the radius than age-matched white female subjects. When the TBCa values were normalized for body size (i.e., corrected for height and lean body mass), the TBCa was still higher for the black women but not as high as the absolute TBCa values. Clearly, it is the larger muscle mass (as reflected by the 40K measure) in relation to weight and height that accounts for this difference. The lower prevalence of fracture and osteoporosis observed in black women relative to white women is due in part to this greater quantity of skeleton. American black women with a higher bone density (i.e., skeletal mass) maintain mechanical integrity of the skeleton longer than individuals with a lower bone density. It is suggested that the larger muscle mass in black women is, in part, a determinant of their increased skeletal mass and is partly responsible for their apparent resistance to osteoporosis and fracture of the skeleton.

Combination therapy for osteoporosis.

The effect of therapy that simultaneously stimulates bone formation and inhibits bone resporption was evaluated in five patients with primary osteoporosis. The technique of in vivo neutron activation analysis was used to measure total body calcium (TB-Ca). The patients were treated with calcium supplements and salmon calcitonin combined with either a low or a high dose of growth hormond (hGH). There was no significant increase in skeletal mass (TB-Ca) during the low-dose hGH regimen. An increase in skeletal mass was observed in all patients following the high-dose regimen, except for one patient who developed secondary hyperparathyroidism. Although this study must be considered to be of a preliminary nature, the magnitude of the response in calcium balance suggests that skeletal mass can be increased in osteoporosis if combination therapy is employed.

Changes in body chemical composition with age measured by total-body neutron activation.

Total-body levels of calcium and phosphorus (reflecting skeletal mass) and total-body levels of potassium (reflecting muscle mass) were measured by neutron activation analysis in 39 men and 40 women ages 30-90 yr. In order to intercompare the total body calcium (TBCa) values in a heterogeneous population, such as this, it was necessary to normalize the data for skeletal size. The normalization consisted of dividing the absolute calcium level by the predicted calcium level for each individual matched to a set of critical parameters. The parameter used in the computation of normal values were age, sex, muscle mass, i.e., total body potassium (TBK) and height. For the calcium data of the women, it was necessary to add an age correction factor after the age of 55 yr. The calcium ratio(mean ratio of the predicted to measured TBCa) in men was 1.000 +/- 7.8% and in women 0.996 +/- 7.1%. The TBCa of normal males and females can thus be predicted to +/- 13% (at the 90% confidence level). An exception to this was found in males (70-90 yr) who exhibited a mean calcium ratio greater than 1.13. The derivative of TBCa with time was determined for this population of men and women by taking into account the dependency of calcium on three time dependent variables, height, TBK, and an explicit age correction factor in the case of the women. The mean rate of loss of TBCa in women was 0.37% and 1.1% per year before and after menopause (50 yr). In the males, the average rate of loss of TBCa was 0.7% per year after 50 yr of age. The pattern of total body phosphorus (TBP) loss with age paralleled that of TBCa as the ratio of TBP/TBCa was rather constant with age. The constancy of the ratio suggests that the mineral composition of bone does not change significantly with age. The rate of loss of TBK with age was also related directly to that of TBCa. The mean ratio of TBK/TBCa was 9.9 in females and 8.0 in males and this ratio remained relatively constant from 30-70 yr. Thus, the mechanism responsible for the loss of bone with age, whether nutritional deficiency or decreased gonadal function and physical activity may also be responsible for the loss of muscle mass with age.

Compartmental body composition of cancer patients by measurement of total body nitrogen, potassium, and water.

Quantitative measurement was made of body composition in patients with several forms of neoplastic disease. Total body nitrogen was determined by means of the prompt gamma neutron activation technique; total body potassium was measured with the use of a whole body counter. The mass and protein content of the muscle compartment and nonmuscle lean tissue were estimated by application of the technique of compartmental analysis. Total body water, determined simultaneously with the use of tritium label, provided a measure of lean body mass. From these data, the body fat can be inferred. The prompt gamma neutron activation and whole body counting techniques represent a considerable advance over the balance and radioisotope techniques used in earlier studies. The new techniques make possible sequential studies over prolonged periods of time with a considerable degree of accuracy. The loss of body weight by patients with solid tumors consisted primarily of the loss of muscle mass and body fat. Even in severe wasting, the patients appear to retain significant amounts of body fat. It is the skeletal muscle which is predominantly lost; the visceral life-supporting system is, to a considerable extent, spared. The nonmuscle tissue including the visceral fraction did not change in this study, and actually appeared to increase in size when comparison was made with the normal contrast population. The loss of total body water was slight in the cancer patients studied.